张战民, 张风春①. 低频率超声对MCF-7/DOX细胞多药耐药逆转的体外研究*[J]. 中国肿瘤临床, 2010, 37(10): 546-549. DOI: 10.3969/j.issn.1000-8179.2010.10.002
引用本文: 张战民, 张风春①. 低频率超声对MCF-7/DOX细胞多药耐药逆转的体外研究*[J]. 中国肿瘤临床, 2010, 37(10): 546-549. DOI: 10.3969/j.issn.1000-8179.2010.10.002
ZHANG Zhanmin1, ZHANG Fengchun2. Reversal Effect of Low-frequency Ultrasound on Multi-drug Resistance in Human Breast Cancer Cell Line MCF-7/DOX in vitro[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(10): 546-549. DOI: 10.3969/j.issn.1000-8179.2010.10.002
Citation: ZHANG Zhanmin1, ZHANG Fengchun2. Reversal Effect of Low-frequency Ultrasound on Multi-drug Resistance in Human Breast Cancer Cell Line MCF-7/DOX in vitro[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(10): 546-549. DOI: 10.3969/j.issn.1000-8179.2010.10.002

低频率超声对MCF-7/DOX细胞多药耐药逆转的体外研究*

Reversal Effect of Low-frequency Ultrasound on Multi-drug Resistance in Human Breast Cancer Cell Line MCF-7/DOX in vitro

  • 摘要: 目的:观察低频率超声空化效应对人乳腺癌细胞株MCF-7/DOX 多药耐药的逆转作用,并探讨其逆转肿瘤多药耐药的机制。方法:以不同的超声辐射时间照射MCF-7/S 、MCF-7/DOX 细胞,采用MTT 法筛选出非细胞毒剂量的超声照射时间。以无毒剂量的超声照射联合不同浓度的DOX,比较单独DOX组与联合组MCF-7/DOX 细胞对DOX的IC 50值有无明显差异,从而判断低频率超声的增敏作用,并计算增敏倍数和相对逆转效率。用流式细胞仪检测细胞凋亡、细胞内阿霉素的浓度。结果:低频率超声辐射对MCF-7/DOX 细胞具有一定的细胞毒作用,其非细胞毒辐射时间是10s。非细胞毒性的超声辐射可显著增加阿霉素对MCF-7/DOX 细胞的抑制率(从21.65%±0.05% 升至43.13%±0.19%),可显著降低阿霉素对MCF-7/DOX 细胞的IC 50 (从61.08± 0.27μg/mL降至 28.12± 5.94μ g/mL);对MCF-7 细胞的抑制率(从66.47% ± 0.02%升至 67.25% ± 0.20%)及IC 50 (从0.84± 0.07μ g/mL 降至 0.802 ±0.03μ g/mL)无明显的影响。低频率超声对MCF-7/DOX 细胞的逆转倍数为2.17倍,相对逆转效率为:54.71% 。流式细胞仪检测结果显示:单独应用DOX,MCF-7 细胞的凋亡率为33.99% ,MCF-7/DOX 细胞的凋亡率为4.4% ,低频率超声与DOX合用后,MCF-7/DOX凋亡率为13.70% 。低频率超声处理后,MCF-7/DOX 细胞内DOX浓度显著增加,峰值明显右移,但尚不能达到敏感细胞的水平。结论:低频率超声可部分逆转人乳腺癌MCF-7/DOX 细胞对阿霉素的耐药性,其逆转机制考虑为低频率超声空化效应增加细胞膜的通透性,增加肿瘤细胞内抗肿瘤药物的浓度,从而杀灭耐药的肿瘤细胞,逆转肿瘤耐药性。

     

    Abstract: Objective:To investigate the effects and mechanism of low-frequency ultrasound in reversing multidrug re -sistance (MDR) in the MCF- 7/DOX cell line. Methods: MTT assay was used to detect the cytotoxic effect of low-frequency ultrasound and the sensitivity to Adriamycin of the MCF-7/DOX cell line. The apoptosis and concentration of Adriamycin in the cells were detected by flow cytometry (FCM). Results: Low-frequency ultrasound had a definite cytotoxic effect on MCF-7 and MCF- 7/DOX cells. The non-cytotoxic time of low-frequency ultrasound was 10 seconds. The non-cytotoxic low-frequency ultrasound significantly increased the inhibitory rate and decreased the half-maximal inhibitory concentration (IC50) value of Adriamycin in the MCF-7/DOX cell line. The IC 50 was significantly reduced from 61.08± 0.27μ g/mL to 28.12±5.94μ g/mL. The non-cytotoxic low-frequency ul trasound could partly reverse MDR in MCF 7/DOX cells by 2.17-fold in-crease. FCM suggested that low-frequency ultrasound combined with DOX could significantly increase the intracellular con centration of Adriamycin and the apoptosis of MCF- 7/DOX. Conclusion:Low-frequency ultrasound can enhance the cytotox -icity of DOX and partially reverse the DOX resistance of MCF- 7/DOX. The mechanism may be related to an increase in the permeability of the cell membrane and the concentration of intracellular DOX and may promote the apoptosis of MCF- 7/ DOX.

     

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